title: Implications of TNF-α in the pathogenesis and management of GVHD.
abstract: Clinical graft-versus-host disease (GVHD) symptoms are the result of a complex set of interactions between cellular and soluble factors. One of the key soluble factors is the proinflammatory cytokine, TNF-α, which participates in the initiating events that culminate in GVHD as well as amplifies the disease process once established. The importance of TNF-α in this process has been supported by a series of clinical experiments demonstrating strong correlation between TNF receptor-1 levels and GVHD. TNF-α has both indirect effects, through activating and proliferation pathways of T cells, the main cellular effector of GVHD, and direct effects leading to apoptosis, on GVHD target tissues. Accordingly, TNF-α has been used as a therapeutic target in experimental GVHD prevention and treatment strategies with promising clinical results. TNF-α can be pharmacologically inhibited using soluble TNF receptors or monoclonal antibodies. The optimal dosing and duration of TNF inhibition to prevent or treat GVHD remains under investigation.
authors.affiliation: University of Michigan Blood and Marrow Transplantation Program, 5303 Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109-5941, USA. jelevine@med.umich.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D006402:Hematologic Diseases / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology* / Q000378:metabolism; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha